Targeted Cancer Therapies
Subtitle: Innovative drugs and their impact on the future of oncology developments.
Publisher: Reuters Business Insight, London
Published: 2005
Place of publication: London, UK
Format: Hardcover
Number of pages: 120
Description: Innovative drugs and their impact on the future of oncology developments

The focus of drug discovery will move away from a small number of mostlychronic diseases that have been traditionally targeted by "big pharma" and towards other, numerous areas of less prevalent diseases. This will, in turn, create a targeted medicines sector and, in time, lead to the development of personalized health maintenance programs, says industry expert Gilbert Mertens in a new report, Targeted Cancer Therapies, written for and published by Reuters Business Insight. 

Companies will find more blockbuster opportunities in other disease markets where there are fewer therapies and a high degree of unmet need, enabling highly innovative products to compete strongly. The oncology, thrombosis, arthritis and respiratory disease markets will see the strongest blockbuster sales growth. 

Cancer therapies offer better opportunities for European players, the report says, noting that whereas five companies - Pfizer, Merck & Co, GlaxoSmithKline, Johnson & Johnson and AstraZeneca generated - 58% of total blockbuster sales. European firms make up four of the top five global oncology players. 

The lack of economies of scale in R&D and the low number of new drugs coming through have led to a reorientation towards more in-licensing instead of in-house innovation. Cancer projects account for 29.3% of total clinical pipeline activity. They also make up almost one third (29%) of all drug discovery deals for which therapeutic focus has been publicly disclosed. 

The implications are that big pharma will have to reduce its reliance on blockbuster products, seeking other more sustainable revenue streams to drive growth or, alternatively, identify licensing, acquisition and alliance strategies to gain access to new products. These strategies will serve to accelerate the development of new cancer therapies, of which targeted and innovative therapies are the fastest growth areas. 
Emerging therapies 

Currently, treatment for cancer depends on: the type of cancer; tumor size, location and stage of disease; and the person's general health. Advances in research have meant that treatment will depend less on cancer type (organ location, histology) and be more driven by molecular features, the report notes.
 
The cancer market can be split into four main groups of drugs: cytotoxics, hormonals, innovative agents and adjunct therapies. Innovatives are the most promising area for all cancers and may create the answer to reduced side effects associated with cancer treatment and have the vast potential of dramatically increasing disease free survival and overall survival rates. The promise behind innovative drugs and reduced side effects arises from the potential of specifically targeting cancer cells, thus avoiding killing normal healthy cells, a common problem associated with cytotoxics and anti-metabolites. 

Advances in diagnosis are critical to the future success of targeted cancer therapies. Many companies developing novel therapies do not sufficiently consider the prior or simultaneous development of accompanying diagnostics that would support their product's marketing, leading to lower uptake or even non-approval/physician skepticism due to use in inappropriate patients. Genentech's Herceptin (trastuzumab) is one recent example of an innovative drug for which the development of an appropriate diagnostic test has proven essential to strong uptake within the breast cancer market and allowed the drug to be appropriately targeted and therefore demonstrate cost-effectiveness for certain patients. 

There has been a clear move away from cytotoxics in favor of cytostatic drugs, which has been integral to the development of targeted cancer therapies. While traditional chemotherapy agents kill cancer cells by being cytotoxic, many new agents work mostly by interrupting their growth, ie, they are cytostatic. 

Therapy area analysis 
For breast cancer, new treatments will be driven by: improved screening techniques; research into the multiple tissue-specific interactions of the estrogen receptor and its response to anti-estrogen therapy; the development of pure anti-estrogen agents which completely block estrogenic activity; and increasing use of cytostatic therapy and combination therapy (of anti-estrogens and aromatase inhibitors).
 
There is still a lack of curative treatments in breast cancer. In particular, there is a need to improve the efficacy of agents in treating cancers that have developed resistance to current cytotoxics and hormonals. Another major issue with current treatments is the toxicity of many of the drugs employed. These challenges present an opportunity for targeted cancer drugs that may reduce the side effect profile and either improve the efficacy of existing drugs or outperform them, the report states. 

Drug treatments for colorectal cancer exhibit similar limitations to those for other cancers in terms of excessive side effects and insufficient survival benefit. In the absence of a curative treatment, there is also a need for agents that can improve the quality of life for patients with unresectable tumors. Existing treatments tend to follow protracted delivery schedules and are expensive. 

The major unmet need with lung cancer is extension of patient survival. Despite significant improvements in pharmacotherapy for lung cancer in the last 20 years, the current five-year survival figure is less than 15%, dramatically less than the rates for other major cancers. 

Need for drugs that offer survival extension 
There is a drastic need for drugs that can offer significant extension in survival and, ideally, extended disease-free survival. There is also a need for improved second-line treatments for patients who fail to respond to first-line treatments, or suffer a relapse after receiving first-line therapy, according to the report. 

While cure rates for early-stage disease are high, there remains a critical unmet need for a curative treatment for advanced metastatic prostate cancer or hormone-refractory prostate cancer. There is also a need for new treatments with fewer side effects than current cytotoxics and hormonals. 

Case studies 
The current key players in targeted therapies are Sanofi-Aventis, Roche (and Genentech) and AstraZeneca. Several companies with established oncology franchises are also investing heavily in targeted therapies. Additionally, pharmaceutical heavyweights such as GlaxoSmithKline and Pfizer, which have traditionally had less exposure in oncology, are also developing new therapies. 

Sanofi-Synthelabo's acquisition of Aventis creates a European oncology heavyweight. While Sanofi has a relatively limited oncology pipeline, Aventis has a current oncology blockbuster (Taxotere; docetaxel) and three promising cancer products currently in Phase III trials: Advexin (a gene therapy), Gastrimmune (prostate cancer vaccine) and Genasense (oblimersen sodium). 

Roche is a key leader in targeted cancer therapies, having focused on becoming an innovative, targeted medicine player. The Swiss firm has a strong cancer pipeline, partly attributable to its collaboration with Genentech. One of Roche's core strengths is its diagnostics business, which will enable it to develop specific diagnostic tests and appropriate tumor markers in parallel with development of targeted therapies. 

AstraZeneca has one of the richest oncology franchises. The company specializes in hormone therapies for breast and prostate cancer, and is highly focused on targeted therapeutics. The company has an important alliance with Array Biopharma and has recently launched Iressa (gefitinib; Marketletters passim), an epidermal growth factor receptor inhibitor, which achieved $228 million sales in 2003 and is forecast to achieve $655 million in 2009. 

On the other hand, oncology represents a new market for Pfizer, with all of its existing marketed products having been acquired via its takeover of Pharmacia. The oncology portfolio is relatively broad, spanning both cytotoxic and hormonal therapies, the report notes. 

Conclusions 
Pharmaceutical companies will introduce three core strategies in order to develop targeted cancer therapies effectively: 

- reduce the cost of drug development and bringing products to market by using strategic alliances and in-licensing and leveraging economies of scale in sales and marketing;

- use genomics to prevent expensive clinical trials on agents with little or no potential: in the long term, genomics is expected to drive down the cost of clinical trials and improve the effectiveness of targeted cancer therapies; and

- maximize patient potential by increasing the number of indications: a number of companies have used success in one indication to drive applications in further indications. This strategy has been employed by Roche/ Genentech with Avastin (bevacizumab) and by AstraZeneca with Iressa. 

Furthermore, improved diagnostics are central to the ongoing development and success of targeted cancer therapies. For example, the success of Roche's Herceptin has been enhanced by the development of screening tests that enable more convenient identification of HER2-positive cancers. 

Euro firms will dominate 
European companies will dominate targeted cancer therapies. Of the main US competitors, only Bristol-Myers Squibb is in the top five global oncology players. European companies also lead in-licensing deals in oncology. However, Eli Lilly and Pfizer are among a number of US firms developing a range of targeted cancer therapies, the report says. 

The arrival of innovative targeted therapies will not make traditional cytotoxic drugs redundant. Rather, targeted therapies and cytotoxics will be used in combination with each other, which will serve to drive the whole cancer market, it concludes.